Poly Brominated Diphenyl Ethers (PBDEs) are known flame retardants with highly persistent and lipophilic in nature. The continued usage of PBDE in various products amplifies the human burden of PBDEs. It is therefore, important to study the potential toxicological and/or biological effects of PBDE exposure in human. In this study we investigated the mode of action of PBDE induced toxicity in human liver by exposing human hepatocarcinoma cells in a time (24-72h) and dose (0-100μM) dependent manner. The highest test dose caused an inhibition in cell viability up to 50% after 72h, whereas lower doses (<50μM) showed slight increase in cell viability. Likewise, higher doses caused significant accumulation of intracellular ROS over time. Further, increase in caspase-3 enzyme levels and DNA fragmentation showed that, lower brominated PBDEs induce liver toxicity through accumulation of toxic metabolites and reactive oxygen species over time leading to caspase-mediated apoptotic cell death.

Graduation date: 1994

Uncoupling protein-2 (UCP2) may be linked to the attenuation of reactive oxygen species (ROS), but it is unclear whether this phenomenon pertains to the pancreatic beta cell. In this study, a UCP2-deficient mouse model was used to assess the importance of UCP2 to beta cell viability. We investigated the effect of UCP2 absence in response to a beta cell cytotoxic model of diabetes induction. In vivo treatment by the cytotoxic agent streptozotocin led to overall beta cell loss, but severity was not exacerbated by UCP2 deficiency. We also examined ROS production and cell viability in islet cells exposed to various stressors associated with oxidative stress. In vitro measurements of ROS and cell death in islet cells demonstrated that the response was not influenced by UCP2 expression. In contrast with UCP2 overexpression studies showing cytoprotection, this study reveals that beta cell survival is not compromised by the absence of UCP2.

To better understand the impact of task conflict in work teams, an incremental, multi-level model is developed, which distinguishes individual-level perceptions of conflict from more overt group-level manifestations of conflict. Task conflict is conceptualized as being detrimental for teams only to the extent that it positively predicts relationship conflict. The positive relationship between task conflict and relationship conflict is referred to as conflict spillover. The composition of team members’ underlying beliefs concerning the functional value of task conflict (referred to as conflict values) is examined as a moderator of conflict spillover. It is proposed that perceptual conflict spillover is smaller among team members who hold positive conflict values, and that manifest conflict spillover is smaller among teams composed primarily of members who hold positive conflict values. Hypotheses were tested in a longitudinal study of 59 student teams (294 individuals). At the team level, the diversity of team members’ conflict values was found to moderate manifest conflict spillover, such that the association between task and relationship conflict was significantly positive for teams composed of members who held more diverse conflict values. For teams composed of members who had less diverse conflict values, there was no significant association between manifest task conflict and manifest relationship conflict. As a result of these significant differences in conflict spillover, manifest task conflict indirectly and negatively predicted the task performance and viability of teams containing more diverse conflict values, but did not significantly impact the effectiveness of teams with less diverse conflict values. At the individual level, the significant positive association between perceived task conflict and perceived relationship conflict was not moderated by individual conflict values. However, because of this perceptual conflict spillover, task conflict perceptions also indirectly and negatively predicted team members’ personal willingness to continue working in the team. Results of this dissertation highlight important differences in the ways that conflict operates at the individual and group levels. Having identified the diversity of conflict values as a moderator of manifest conflict spillover, this dissertation outlines areas for further academic and practical knowledge development concerning the prevention of dysfunctional team dynamics.

Uncoupling protein-2 (UCP2) may be linked to the attenuation of reactive oxygen species (ROS), but it is unclear whether this phenomenon pertains to the pancreatic beta cell. In this study, a UCP2-deficient mouse model was used to assess the importance of UCP2 to beta cell viability. We investigated the effect of UCP2 absence in response to a beta cell cytotoxic model of diabetes induction. In vivo treatment by the cytotoxic agent streptozotocin led to overall beta cell loss, but severity was not exacerbated by UCP2 deficiency. We also examined ROS production and cell viability in islet cells exposed to various stressors associated with oxidative stress. In vitro measurements of ROS and cell death in islet cells demonstrated that the response was not influenced by UCP2 expression. In contrast with UCP2 overexpression studies showing cytoprotection, this study reveals that beta cell survival is not compromised by the absence of UCP2.

To better understand the impact of task conflict in work teams, an incremental, multi-level model is developed, which distinguishes individual-level perceptions of conflict from more overt group-level manifestations of conflict. Task conflict is conceptualized as being detrimental for teams only to the extent that it positively predicts relationship conflict. The positive relationship between task conflict and relationship conflict is referred to as conflict spillover. The composition of team members’ underlying beliefs concerning the functional value of task conflict (referred to as conflict values) is examined as a moderator of conflict spillover. It is proposed that perceptual conflict spillover is smaller among team members who hold positive conflict values, and that manifest conflict spillover is smaller among teams composed primarily of members who hold positive conflict values. Hypotheses were tested in a longitudinal study of 59 student teams (294 individuals). At the team level, the diversity of team members’ conflict values was found to moderate manifest conflict spillover, such that the association between task and relationship conflict was significantly positive for teams composed of members who held more diverse conflict values. For teams composed of members who had less diverse conflict values, there was no significant association between manifest task conflict and manifest relationship conflict. As a result of these significant differences in conflict spillover, manifest task conflict indirectly and negatively predicted the task performance and viability of teams containing more diverse conflict values, but did not significantly impact the effectiveness of teams with less diverse conflict values. At the individual level, the significant positive association between perceived task conflict and perceived relationship conflict was not moderated by individual conflict values. However, because of this perceptual conflict spillover, task conflict perceptions also indirectly and negatively predicted team members’ personal willingness to continue working in the team. Results of this dissertation highlight important differences in the ways that conflict operates at the individual and group levels. Having identified the diversity of conflict values as a moderator of manifest conflict spillover, this dissertation outlines areas for further academic and practical knowledge development concerning the prevention of dysfunctional team dynamics.

Recently, it has been suggested that neurodevelopmental abnormalities underlie schizophrenia. However, it has also been suggested that schizophrenia is a neurodegenerative disease as evidenced by a progressive worsening of symptoms over time. Neurodevelopmental abnormalities may, therefore, create a functionally compromised system that is more susceptible to neuronal atrophy and/or death caused by environmental factors such as stress (a known precipitant of acute psychotic episodes and exacerbant of schizophrenia). This hypothesis was tested using the putative neurodevelopmental model of schizophrenia described by Lipska 'et al'. (1993). The effects of neonatal hippocampal lesions on BDNF mRNA and NMDAR1 mRNA, factors involved in development, cell survival and cell communication, were investigated in adult rats following exposure to a physiological stressor. Apoptosis levels were also investigated in these rats to determine if neurodegeneration was present. Results demonstrate that BDNF mRNA was reduced in the prefrontal cortex and hippocampus of lesioned as compared to sham rats. Increased BNDF mRNA resulted from swim stress in both groups, but the increase in lesioned animals was more pronounced than controls. NMDAR1 mRNA was also reduced in the prefrontal cortex and CA3 and CA1 regions of the hippocampus in lesioned versus sham rats. There was an increase, however, in the dentate gyrus of lesioned versus sham rats. Swim stress increased NMDAR1 mRNA in the prefrontal cortex and decreased it in the hippocampus. There was also an increase in apoptosis in lesioned versus sham rats, with no significant increase in response to stress. Reductions in BDNF mRNA in lesioned versus control animals support the hypothesis that neurodevelopmental lesions may result in a system more susceptible to stressors. Reductions in NMDAR1 mRNA are in accordance with the NMDA glutamate receptor hypofunction theory of schizophrenia. It is possible that reductions in glutamate function can remove the inhibitory effect of GABA, thereby resulting in overexcitation of the system and a potential for neurodegeneration. Increased apoptosis supports the presence of neurodegeneration as an ongoing phenomenon. Even though the effect of acute stress on apoptosis was not significant, the very small increases demonstrated can have significant functional consequences over extended periods of time.

Imaging of myocardial viability using the delayed enhancement technique currently provides high image contrast between infarcted and normal tissue with the aid of a magnetization prepared fast gradient echo pulse sequence following the administration of an extracellular contrast agent. However, there exists a degree of image contrast variability and subjectivity due to contrast agent kinetics and user-specified imaging parameters. Also, the technique has not been explored at higher field strengths (3T), which offer greater inherent signal-to-noise ratio. The overall goal of this study is to compare magnetic resonance delayed contrast enhancement of myocardial infarction at 1.5T and 3T. The analysis was conducted by first developing a comprehensive mathematical simulation of the imaging sequence, which allowed modification of various imaging parameters. Simulations were performed to optimize the sequence for flip angle and inversion time, as well as to evaluate the influence of other image parameters that affected contrast. These theoretical results were validated experimentally with phantoms. In vivo post-contrast T1 measurements at 1.5T and 3T from normal volunteers (n=10) and patients (n=5) provided more precise input into mathematical optimization simulations. In both populations, longer T1 values were found at 3T compared to 1.5T for normal (pre-contrast: 1.24 .06s vs. 1.07 .05s; post-contrast: 0.34-0.59 vs. 0.33-0.54s, n=15) and infarcted myocardium (pre-contrast: 1.27 .06s vs. 1.04 .06s; post-contrast: 0.25-0.37s vs. 0.23-0.32s, n=5). Corresponding simulations using these T1 values revealed an infarct-to-normal tissue contrast gain at 3T of approximately 25%. In vivo image contrast between infarcted and normal tissue following contrast administration was also higher at 3T by approximately 37%. In conclusion, there was good correlation between mathematical simulations of delayed enhancement and experimental results, enabling parameters to be compared and optimized offline given input T1 values. Although contrast-enhanced viability imaging at 3T suffered from artifacts due to field, RF, and inversion pulse inhomogeneity, these results suggest that 3T offers higher contrast-to-noise ratio than 1.5T for this application.

Recently, Web 2.0 tools and technologies are widely adopted by organizations. This phenomenon drives attention and discussion on the intention of adoption and usage of such tools within enterprises. The purpose of this study was to explore the intention of enterprise to adopt Web 2.0 technologies for internal collaboration, using the fit-viability model that takes into consideration the degree of fitness between technological tools and the collaboration tasks, and the feasibility of implementation. In this research, a more comprehensive model to evaluate the intention to adopt Collaboration 2.0 tools and major factors identified from previous studies were developed. An empirical survey was conducted and 347 valid observations were collected. Results from the data analysis reveal that both the fit between task and technology and organizational viability have positive effects on organizational adoption of the collaboration 2.0 tool.

Assessment of sperm viability is an important component for evaluating stallion sperm quality. The flow cytometer is considered the standard in the assessment of sperm plasma membrane integrity (viability); however, this instrument is costly to purchase and use, and it requires an experienced technician to operate it. The growing practice of assisted reproductive technologies (ARTs) in the equine industry has increased the need for an accurate but cost-effective means of determining sperm membrane viability. The NucleoCounter® SP-100TM is reported to be an accurate, easy-to-perform, and an efficient stallion-side test for sperm membrane viability. To evaluate usefulness of the NucleoCounter® SP-100TM for assessing sperm membrane integrity, neat semen was subjected to four treatments with varying seminal plasma volumes and sperm concentrations. Sperm membrane viability was assessed immediately, and at 24 and 48 hours after cooled-storage using three methods: 1) flow cytometer utilizing the fluorescent vital stains SYBR-14/propidium iodide; 2) NucleoCounter® SP-100TM utilizing the fluorescent vital stain propidium iodide; 3) eosin-nigrosin stained air-dried smears of semen. Sperm motion characteristics (total and progressive motility) were assessed using a computer assisted sperm motion analyzer (CASMA) and results were compared to sperm membrane viability to determine the relationship between sperm membrane viability and motion characteristics. Results were compared statistically by: 1) analysis of variance (ANOVA); 2) linear regression analysis; 3) coefficient of variation on untransformed and transformed data (arc sine square root); and 3) the agreement of two instruments, by means of which the difference between measurements of the two instruments were plotted on the y-axis and the average of measurements from the two instruments were plotted on the x-axis. Results obtained with the NucleoCounter® SP-100TM agreed best with the flow cytometer, and least with eosin-nigrosin staining. Coefficients of variation were ≤ 5% for the three methods (transformed data). Sperm motion characteristics and sperm viability were similar among treatments at Time 0. At Times 24 and 48, sperm motion characteristics decreased at a more significant rate compared to viability in the treatments containing ≥ 50% seminal plasma, whereas differences among treatments were only significant at seminal plasma concentrations above 50% when only sperm membrane viability was considered.